Acyl isocyanate

Reaction of 2-aminothiazoles with alkyl isocyanates yields 2-thiazolylureas (256) (Scheme 153) (479-483). This reaction is general and works with acyl isocyanates (484. 485). These heterocyclic ureas are also prepared by the reaction of H2O on 2-thia2olylcyanamide (486) or by action of HjOj on the corresponding thiourea (303, 481). 

Acyl isocyanates (13,X = O, S) have been shown to react as heterodienes ia most cycloadduct formations. Notable examples iaclude autodimerization and the addition to imines (46,47). Unlike aromatic isocyanates, it is not possible to predict the reaction pathway nor the stmcture of the products which may arise from a given approach or set of reaction conditions. 

Conversely, acyl isocyanates yield dimers which include the C=X (16) moiety (where X =0, S, NR) in the product ring stmcture (56). 

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic appHcations, caimot be direcdy synthesized from amides and phosgene. Reactions of acid haUdes with cyanates have been suggested. However, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride [79-37-8]. CycHc intermediates have been observed in these reactions which generally give a high yield of the desired products (86). 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

Acylurea derivatives are readily prepared in one step by addition of amines to acyl isocyanates in high yields (Eqs. 1 and 2)14>. 

When the substrate is oxalyl chloride (ClCOCOCl) and the reagent an unsubstituted amide, an acyl isocyanate (RCONCO) is formed. The normal product (RCONH-COCOCl) does not form, or if it does, it rapidly loses CO and HC1. ° ... 

When the reagent is the thiocyanate ion, S-alkylation is an important side reaction (10-43), but the cyanate ion practically always gives exclusive N-alkylation. ° Primary alkyl halides have been converted to isocyanates by treatment with sodium nitrocyanamide (NaNCNN02) and m-chloroperoxybenzoic acid, followed by heating of the initially produced RN(N02)CN. ° When alkyl halides are treated with NCO in the presence of ethanol, carbamates can be prepared directly (see 16-7). ° Acyl halides give the corresponding acyl isocyanates and isothiocyanates. For the formation of isocyanides, see 10-111. 

Salts of aliphatic or aromatic carboxylic acids can be converted to the corresponding nitriles by heating with BrCN or CICN. Despite appearances, this is not a substitution reaction. When R COO was used, the label appeared in the nitrile, not in the C02, and optical activity in R was retained. The acyl isocyanate... 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

The reaction of the biacetyl-trimethyl phosphite adduct (65) with acyl isocyanates has been extended to the isocyanates ROCONCO and PhCS-NCO.46 With the thiazolin-4,5-diones (66), (65) gave the thiazol-4-ones (67). 

One principal access to 1,2,4-oxadiazoles consists of N—O bond formation by electrocyclic ring closure of nitrenoids N—CR —N—CR =0. For instance, heating acyl isocyanates (159) with trimethylsilyl azide alfords high yields of 1,2,4-oxadiazoles (Scheme 68) <79JCS(P1)185,80JOC5130). Similarly, elimination of HCl from A -chloroamidines (160) (Scheme 69) <84BCJ1I6> and ther-... 

Silyl-substituted diazoketones 29 cycloadd with aryl isocyanates to form 1,2,3-triazoles 194 (252) (Scheme 8.44). This reaction, which resembles the formation of 5-hydroxy-l,2,3-triazoles 190 in Scheme 8.43, has no analogy with other diazocarbonyl compounds. The beneficial effect of the silyl group in 29 can be seen from the fact that related diazomethyl-ketones do not react with phenyl isocyanate at 70 °C (252). Although the exact mechanistic details are unknown, one can speculate that the 2-siloxy-1-diazo-1-alkene isomer 30 [rather than 29 (see Section 8.1)] is involved in the cycloaddition step. With acyl isocyanates, diazoketones 29 cycloadd to give 5-acylamino-l,2,3-thiadiazoles 195 by addition across the C=S bond (252), in analogy with the behavior of diazomethyl-ketones and diazoacetates (5). 

Bei dieser Aufbauvariante des 1,2,4-Oxadiazol-Ringes stellt die Komponente O—C — N-C den Teil eines Acyl-isocyanates dar, das mit Azido-trimethyl-silan als N-Lieferant formal das Het-aren bildet. 

Cycloaddition Reactions of Aliphatic and Aromatic Acyl Isocyanates B. A. Arbuzov and N. N. Zobova, Synthesis, 1974, 461-476. 

The procedure may be adapted for the preparation of other acyl isocyanates (i.e., dichloroacetyl, trichloroacetyl, phenyl-acetyl, diphenylacetyl, benzoyl, etc) and is generally more convenient than the reaction of acid chlorides with silver cyan-ate3 4 Acyl isocyanates react with amines, alcohols, and mer-captans to yield acyl ureas, carbamates, and thiocarbamates. 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

Oxo derivatives of 4//-l,3-oxazine can readily be obtained from acetylenic compounds and acyl isocyanates, e.g., to obtain 62169 in 85% yield. This is a [2 + 4] cycloaddition [Eq. (49)]. A number of 4//-1,3-oxazin-4-ones have been prepared by this method.169 194"197... 

Acyl isocyanates can also react with ketene to give derivatives of 4/f-l,3-oxazine (63)172 [Eq. (50)]. 

The reaction of acyl isocyanates and a>-cyano alkylazides affords fused products via the postulated thiatriazoline intermediate 75. Then, the masked 1,3-dipole oxathiazoline 76 is generated, and intramolecular reaction takes place, affording the fused 1,2,4-thiadiazole derivatives 77 (Scheme 16) <1993J(P1)27>. 

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